The objective of the proposed research is to continue a systematic investigation of the biotransformation of drugs and foreign chemicals (xenobiotics) in tissues of the human foeto-placental unit at various gestational stages, Special consideration will be given to the analysis of NADPH-dependent mixed-function oxidation reactions involving xenobiotics, steroids and lipids and studies of the interrelationships among these metabolic processes. An attempt will be made to define the characteristics of placental fetal hepatic and fetal adrenal cytochrome P-450 in terms of their spectral properties, catalytic functions, and pharmacologic-physiologic roles. Conjugation-hydrolysis reactions and their possible relationsips to the transport of drugs between maternal and fetal circulations also will be studied in greater detail. The importance of such studies is indicated by the known role of environmental chemicals (including drugs and other xenobiotics) as principal interacting etiologic factors in the emanation of birth defects in humans. The drug-metabolizing capacity of the placenta and fetus would be expected to be an impotant determinant of the pharmacologic-toxicologic effects of drugs on the developing conceptus as well as on the pregnant female. The long-term research objective is to provide a better understanding of the basic mechanisms of placental function such that a more rational approach to drug therapy in the pregnant woman, unborn, and newborn child might be developed.